The overall goal of this SBIR is to identify small molecules that can perturb ribosomal frameshifting at the gag-pol junction in HIV- 1 - These may have practical applications, e.g. in the treatment of individuals infected with HIV- 1. The approach involves the screening of natural product extract libraries and synthetic compounds for agents that can perturb frameshifting in a model system predictive of frameshifting behavior during HIV-1 replication. Those extracts found to affect frameshifting will be subjected to bioassay-guided fractionation to permit isolation of the active principle(s). These principles will be obtained in quantities sufficient for evaluation as anti HIV-1 agents and characterized to evaluate their biological properties. If we are able to identify agents that perturb ribosomal frameshifting at the gag-poljunction and thereby affect HIV-1 replication, the effort will be expanded to conduct a focused search for agents potentially efficacious in the treatment of HIV- 1 infection. PROPOSED COMMERCIAL APPLICATIONS: This technology is intended to lead to agents that can be utilized therapeutically for the treatment of HIV-1 -infected individuals.